Field
Exemplary embodiments relate to a method for treating a neurodegenerative disease or depression, the method comprising administering to a subject in need thereof an effective amount of derivatives of 2-amino-2-(1-dodecyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol. More particularly, exemplary embodiments relate to a method for treating a neurodegenerative disease or depression, the method comprising administering to a subject in need thereof an effective amount of derivatives of 2-amino-2-(1-dodecyl-1H-1,2,3-triazol-4-yl)propane-1,3-diol which possess an effect of inhibiting ASM activity.
Discussion of the Background
Sphingolipid metabolism controls normal cell signaling, and abnormal changes in sphingolipid metabolism affect a variety of neurodegenerative diseases including Alzheimer's disease. Meanwhile, ASM (acid sphingomyelinase), an enzyme that regulates sphingolipid metabolism, is a protein which is expressed in almost all kinds of cells and plays an important role in sphingolipid metabolism and cell membrane turnover.
According to previous studies by the present inventors, it was found that the activity of ASM is increased in various neurodegenerative diseases including Alzheimer's disease, and ASM inhibition can thus be a new approach for treating neurodegenerative diseases. It was recently reported that the activity of ASM is increased in neurological diseases such as depression, and that the suppression of ASM is effective in ameliorating the severity of depression (Nature medicine, 2013 Jul. 19(7):934-938, PLoS One 2016 Sep. 6; 11(9): e0162498). Therefore, the development of ASM inhibitors is promising as a useful method for treating various ASM-increased diseases including neurodegenerative diseases.
By the way, to date, some inhibitors which may indirectly inhibit ASM have been identified, while no direct ASM inhibitors have been developed. First, tricyclic antidepressants (e.g., amitriptyline (AMI), desipramine, imipramine, etc.), which are most commonly used as indirect inhibitors of ASM, are used in clinical practice as antidepressant drugs. Although not initially developed as ASM inhibitors, various studies have demonstrated that these drugs exhibit ASM inhibitory effects. The main mode of action of tricyclic antidepressants is the increase of neurotransmitter activity by inhibiting the reabsorption of neurotransmitters in neurons, with the side effect of suppressing ASM. However, in the case of tricyclic antidepressant drugs, it is necessary to develop a novel inhibitor compound of ASM activity since it acts on the nervous system and neurons and may cause adverse side effects such as blurring, increased light sensitivity, and vomiting.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the inventive concept, and, therefore, it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.